3r6i - Revision history

OCA at 10:52, 21 February 2024

OCA — Wed, 21 Feb 2024 10:52:40 GMT

←Older revision		Revision as of 10:52, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3r6i' size='340' side='right'caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='3r6i' size='340' side='right'caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R6I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R6I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.95Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3r43\|3r43]], [[3r58\|3r58]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [https://pdbe.org/3r6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [https://www.ebi.ac.uk/pdbsum/3r6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6i ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [https://pdbe.org/3r6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [https://www.ebi.ac.uk/pdbsum/3r6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.	+	[https://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Aldo-keto reductase 1C3 (AKR1C3) catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs) are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid), arylpropionic acids (flurbiprofen, ibuprofen, naproxen), and indomethacin analogues (indomethacin, sulindac, zomepirac). The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens the base of structures available for future structure-guided drug discovery efforts.	+
-		+
-	Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.,Flanagan JU, Yosaatmadja Y, Teague RM, Chai MZ, Turnbull AP, Squire CJ PLoS One. 2012;7(8):e43965. doi: 10.1371/journal.pone.0043965. Epub 2012 Aug 28. PMID:22937138<ref>PMID:22937138</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3r6i" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
-	*[[Prostaglandin F synthase\|Prostaglandin F synthase]]	+	*[[Prostaglandin F synthase 3D structures\|Prostaglandin F synthase 3D structures]]
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Flanagan~~, J U~~]]	+	[[Category: Flanagan JU]]
-	[[Category: Squire~~, C J~~]]	+	[[Category: Squire CJ]]
-	[[Category: Teague~~, R M~~]]	+	[[Category: Teague RM]]
-	[[Category: Yosaatmadja, Y]]	+	[[Category: Yosaatmadja Y]]
-	~~[[Category: Aldo-keto reductase]]~~	+
-	~~[[Category: Nitro reductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Tim barrel~~]]	+

OCA at 05:50, 15 June 2022

OCA — Wed, 15 Jun 2022 05:50:58 GMT

←Older revision		Revision as of 05:50, 15 June 2022
Line 1:		Line 1:

	==AKR1C3 complex with meclofenamic acid==		==AKR1C3 complex with meclofenamic acid==
-	<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='3r6i' size='340' side='right'caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3R6I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R6I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3r43\|3r43]], [[3r58\|3r58]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [~~http~~://pdbe.org/3r6i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3r6i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6i ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [https://pdbe.org/3r6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [https://www.ebi.ac.uk/pdbsum/3r6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.	+	[[https://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Flanagan, J U]]		[[Category: Flanagan, J U]]
	[[Category: Squire, C J]]		[[Category: Squire, C J]]

OCA at 16:01, 5 August 2016

OCA — Fri, 05 Aug 2016 16:01:43 GMT

←Older revision		Revision as of 16:01, 5 August 2016
Line 1:		Line 1:
		+
	==AKR1C3 complex with meclofenamic acid==		==AKR1C3 complex with meclofenamic acid==
	<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [http://www.ebi.ac.uk/pdbsum/3r6i PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [http://pdbe.org/3r6i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [http://www.ebi.ac.uk/pdbsum/3r6i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3r6i" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 20:06, 25 December 2014

OCA — Thu, 25 Dec 2014 20:06:27 GMT

←Older revision		Revision as of 20:06, 25 December 2014
Line 2:		Line 2:
	<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R6I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R6I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [http://www.ebi.ac.uk/pdbsum/3r6i PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [http://www.ebi.ac.uk/pdbsum/3r6i PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Flanagan, J U.]]	+	[[Category: Human]]
-	[[Category: Squire, C J.]]	+	[[Category: Flanagan, J U]]
-	[[Category: Teague, R M.]]	+	[[Category: Squire, C J]]
-	[[Category: Yosaatmadja, Y.]]	+	[[Category: Teague, R M]]
		+	[[Category: Yosaatmadja, Y]]
	[[Category: Aldo-keto reductase]]		[[Category: Aldo-keto reductase]]
	[[Category: Nitro reductase]]		[[Category: Nitro reductase]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
	[[Category: Tim barrel]]		[[Category: Tim barrel]]

OCA at 06:41, 5 November 2014

OCA — Wed, 05 Nov 2014 06:41:48 GMT

←Older revision		Revision as of 06:41, 5 November 2014
Line 1:		Line 1:
-	[[~~Image:~~3r6i.~~jpg~~\|~~left~~\|~~200px~~]]	+	==AKR1C3 complex with meclofenamic acid==
		+	<StructureSection load='3r6i' size='340' side='right' caption='[[3r6i]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3r6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R6I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r43\|3r43]], [[3r58\|3r58]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r6i RCSB], [http://www.ebi.ac.uk/pdbsum/3r6i PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldo-keto reductase 1C3 (AKR1C3) catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs) are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid), arylpropionic acids (flurbiprofen, ibuprofen, naproxen), and indomethacin analogues (indomethacin, sulindac, zomepirac). The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens the base of structures available for future structure-guided drug discovery efforts.

-	<!--	+	Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.,Flanagan JU, Yosaatmadja Y, Teague RM, Chai MZ, Turnbull AP, Squire CJ PLoS One. 2012;7(8):e43965. doi: 10.1371/journal.pone.0043965. Epub 2012 Aug 28. PMID:22937138<ref>PMID:22937138</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3r6i"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet~~)	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3r6i\| PDB=3r6i \| SCENE= }}~~	+

-	~~===AKR1C3 complex with meclofenamic acid===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	==~~About this Structure~~==	+	*[[Prostaglandin F synthase\|Prostaglandin F synthase]]
-	[[~~3r6i~~]] ~~is a 1 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA].~~	+	== References ==
-	~~[[Category: Homo sapiens]]~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Flanagan, J U.]]		[[Category: Flanagan, J U.]]
	[[Category: Squire, C J.]]		[[Category: Squire, C J.]]

OCA at 19:22, 2 May 2012

OCA — Wed, 02 May 2012 19:22:17 GMT

←Older revision		Revision as of 19:22, 2 May 2012
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-	~~'''Unreleased structure'''~~	+	[[Image:3r6i.jpg\|left\|200px]]

-	The ~~entry 3r6i~~ is ~~ON HOLD~~ ~~until Apr 28 2013~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3r6i", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3r6i\| PDB=3r6i \| SCENE= }}

-	~~Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.~~	+	===AKR1C3 complex with meclofenamic acid===

-	~~Description~~: ~~AKR1C3~~ complex ~~with meclofenamic acid~~	+
		+	==About this Structure==
		+	[[3r6i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R6I OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Flanagan, J U.]]
		+	[[Category: Squire, C J.]]
		+	[[Category: Teague, R M.]]
		+	[[Category: Yosaatmadja, Y.]]
		+	[[Category: Aldo-keto reductase]]
		+	[[Category: Nitro reductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Tim barrel]]

OCA at 05:30, 4 April 2012

OCA — Wed, 04 Apr 2012 05:30:49 GMT

←Older revision		Revision as of 05:30, 4 April 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3r6i is ON HOLD until ~~Paper Publication~~	+	The entry 3r6i is ON HOLD until Apr 28 2013

	Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.		Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.

	Description: AKR1C3 complex with meclofenamic acid		Description: AKR1C3 complex with meclofenamic acid

OCA at 05:03, 25 May 2011

OCA — Wed, 25 May 2011 05:03:18 GMT

←Older revision		Revision as of 05:03, 25 May 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3r6i is ON HOLD	+	The entry 3r6i is ON HOLD until Paper Publication

	Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.		Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.

	Description: AKR1C3 complex with meclofenamic acid		Description: AKR1C3 complex with meclofenamic acid

OCA: Protected "3r6i" [edit=sysop:move=sysop]

OCA — Wed, 30 Mar 2011 07:49:49 GMT

Protected "3r6i" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:49, 30 March 2011

OCA: New page: '''Unreleased structure''' The entry 3r6i is ON HOLD Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J. Description: AKR1C3 complex with meclofenamic acid

OCA — Wed, 30 Mar 2011 07:49:48 GMT

New page: '''Unreleased structure''' The entry 3r6i is ON HOLD Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J. Description: AKR1C3 complex with meclofenamic acid

New page

'''Unreleased structure'''

The entry 3r6i is ON HOLD

Authors: Yosaatmadja, Y., Teague, R.M., Flanagan, J.U., Squire, C.J.

Description: AKR1C3 complex with meclofenamic acid